Characterization of novel RS1 exonic deletions in juvenile X-linked retinoschisis

Leera D'Souza, Catherine Cukras, Christian Antolik, Candice Craig, Ji-Yun Lee, Hong He, Shibo Li, Nizar Smaoui, James F. Hejtmancik, Paul A. Sieving, Xinjing Wang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: X-linked juvenile retinoschisis (XLRS) is a vitreoretinal dystrophy characterized by schisis (splitting) of the inner layers of the neuroretina. Mutations within the retinoschisis (RS1) gene are responsible for this disease. The mutation spectrum consists of amino acid substitutions, splice site variations, small indels, and larger genomic deletions. Clinically, genomic deletions are rarely reported. Here, we characterize two novel full exonic deletions: one encompassing exon 1 and the other spanning exons 4-5 of the RS1 gene. We also report the clinical findings in these patients with XLRS with two different exonic deletions. Methods: Unrelated XLRS men and boys and their mothers (if available) were enrolled for molecular genetics evaluation. The patients also underwent ophthalmologic examination and in some cases electroretinogram (ERG) recording. All the exons and the flanking intronic regions of the RS1 gene were analyzed with direct sequencing. Two patients with exonic deletions were further evaluated with array comparative genomic hybridization to define the scope of the genomic aberrations. After the deleted genomic region was identified, primer walking followed by direct sequencing was used to determine the exact breakpoints. Results: Two novel exonic deletions of the RS1 gene were identified: one including exon 1 and the other spanning exons 4 and 5. The exon 1 deletion extends from the 5′ region of the RS1 gene (including the promoter) through intron 1 (c.(-35)-1723_c.51+2664del4472). The exon 4-5 deletion spans introns 3 to intron 5 (c.185-1020_c.522+1844del5764). Conclusions: Here we report two novel exonic deletions within the RS1 gene locus. We have also described the clinical presentations and hypothesized the genomic mechanisms underlying these schisis phenotypes.

Original languageEnglish
Pages (from-to)2209-2216
Number of pages8
JournalMolecular Vision
Volume19
Publication statusPublished - 2013 Nov 7

Fingerprint

Retinoschisis
Exons
Introns
Genes
Mutation
Comparative Genomic Hybridization
Gene Deletion
Amino Acid Substitution
Walking
Molecular Biology
Mothers
Phenotype

ASJC Scopus subject areas

  • Ophthalmology

Cite this

D'Souza, L., Cukras, C., Antolik, C., Craig, C., Lee, J-Y., He, H., ... Wang, X. (2013). Characterization of novel RS1 exonic deletions in juvenile X-linked retinoschisis. Molecular Vision, 19, 2209-2216.

Characterization of novel RS1 exonic deletions in juvenile X-linked retinoschisis. / D'Souza, Leera; Cukras, Catherine; Antolik, Christian; Craig, Candice; Lee, Ji-Yun; He, Hong; Li, Shibo; Smaoui, Nizar; Hejtmancik, James F.; Sieving, Paul A.; Wang, Xinjing.

In: Molecular Vision, Vol. 19, 07.11.2013, p. 2209-2216.

Research output: Contribution to journalArticle

D'Souza, L, Cukras, C, Antolik, C, Craig, C, Lee, J-Y, He, H, Li, S, Smaoui, N, Hejtmancik, JF, Sieving, PA & Wang, X 2013, 'Characterization of novel RS1 exonic deletions in juvenile X-linked retinoschisis', Molecular Vision, vol. 19, pp. 2209-2216.
D'Souza L, Cukras C, Antolik C, Craig C, Lee J-Y, He H et al. Characterization of novel RS1 exonic deletions in juvenile X-linked retinoschisis. Molecular Vision. 2013 Nov 7;19:2209-2216.
D'Souza, Leera ; Cukras, Catherine ; Antolik, Christian ; Craig, Candice ; Lee, Ji-Yun ; He, Hong ; Li, Shibo ; Smaoui, Nizar ; Hejtmancik, James F. ; Sieving, Paul A. ; Wang, Xinjing. / Characterization of novel RS1 exonic deletions in juvenile X-linked retinoschisis. In: Molecular Vision. 2013 ; Vol. 19. pp. 2209-2216.
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abstract = "Purpose: X-linked juvenile retinoschisis (XLRS) is a vitreoretinal dystrophy characterized by schisis (splitting) of the inner layers of the neuroretina. Mutations within the retinoschisis (RS1) gene are responsible for this disease. The mutation spectrum consists of amino acid substitutions, splice site variations, small indels, and larger genomic deletions. Clinically, genomic deletions are rarely reported. Here, we characterize two novel full exonic deletions: one encompassing exon 1 and the other spanning exons 4-5 of the RS1 gene. We also report the clinical findings in these patients with XLRS with two different exonic deletions. Methods: Unrelated XLRS men and boys and their mothers (if available) were enrolled for molecular genetics evaluation. The patients also underwent ophthalmologic examination and in some cases electroretinogram (ERG) recording. All the exons and the flanking intronic regions of the RS1 gene were analyzed with direct sequencing. Two patients with exonic deletions were further evaluated with array comparative genomic hybridization to define the scope of the genomic aberrations. After the deleted genomic region was identified, primer walking followed by direct sequencing was used to determine the exact breakpoints. Results: Two novel exonic deletions of the RS1 gene were identified: one including exon 1 and the other spanning exons 4 and 5. The exon 1 deletion extends from the 5′ region of the RS1 gene (including the promoter) through intron 1 (c.(-35)-1723_c.51+2664del4472). The exon 4-5 deletion spans introns 3 to intron 5 (c.185-1020_c.522+1844del5764). Conclusions: Here we report two novel exonic deletions within the RS1 gene locus. We have also described the clinical presentations and hypothesized the genomic mechanisms underlying these schisis phenotypes.",
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AU - He, Hong

AU - Li, Shibo

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AU - Sieving, Paul A.

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N2 - Purpose: X-linked juvenile retinoschisis (XLRS) is a vitreoretinal dystrophy characterized by schisis (splitting) of the inner layers of the neuroretina. Mutations within the retinoschisis (RS1) gene are responsible for this disease. The mutation spectrum consists of amino acid substitutions, splice site variations, small indels, and larger genomic deletions. Clinically, genomic deletions are rarely reported. Here, we characterize two novel full exonic deletions: one encompassing exon 1 and the other spanning exons 4-5 of the RS1 gene. We also report the clinical findings in these patients with XLRS with two different exonic deletions. Methods: Unrelated XLRS men and boys and their mothers (if available) were enrolled for molecular genetics evaluation. The patients also underwent ophthalmologic examination and in some cases electroretinogram (ERG) recording. All the exons and the flanking intronic regions of the RS1 gene were analyzed with direct sequencing. Two patients with exonic deletions were further evaluated with array comparative genomic hybridization to define the scope of the genomic aberrations. After the deleted genomic region was identified, primer walking followed by direct sequencing was used to determine the exact breakpoints. Results: Two novel exonic deletions of the RS1 gene were identified: one including exon 1 and the other spanning exons 4 and 5. The exon 1 deletion extends from the 5′ region of the RS1 gene (including the promoter) through intron 1 (c.(-35)-1723_c.51+2664del4472). The exon 4-5 deletion spans introns 3 to intron 5 (c.185-1020_c.522+1844del5764). Conclusions: Here we report two novel exonic deletions within the RS1 gene locus. We have also described the clinical presentations and hypothesized the genomic mechanisms underlying these schisis phenotypes.

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